Human male volunteers were studied in a metabolic facility whilst they were
fed randomized controlled diets. In eight volunteers there was a significa
nt increase in faecal apparent total N-nitroso compounds (ATNC) and nitrite
excretion (P < 0.0001 and P = 0.046, respectively) when randomized doses o
f meat were increased from 0 to 60, 240 and 420 g/day over 10 day periods.
Mean (+/- SE) faecal ATNC levels were 54 +/- 7 <mu>g/day when the diets con
tained no meat, 52 +/- 11 mug/day when the diets contained 60 g meat/ day,
159 +/- 33 mug/day with 240 g meat and 199 +/- 36 mug/ day with 420 g meat,
Higher concentrations of NOC were associated with longer times of transit
in the gut (r = 0.55, P = 0.001) and low faecal weight (r = -0.51, P = 0.00
4). There was no significant decline in levels in individuals fed 420 g mea
t for 40 days. The exposures found on the higher meat diets were comparable
with other sources of N-nitroso compounds (NOC), such as tobacco smoke. Ma
ny NOC are known large bowel initiators and promoters in colon cancer, indu
cing G-->A transitions in codons 12 and 13 of K-ras, Endogenous NOC formati
on, combined with prolonged transit times in the gut, may explain the epide
miological associations between high meat/low fibre diets and colorectal ca
ncer risk.